The long-term goal of this research is two-fold. To elucidate the formation of synaptic contacts during development,on the one hand, and on the other, to study some of the following aspects of synaptic transmission: the functional significance of adrenergic innervation, and of a dual synapse (electrical and chemical), and regulation of acetylcholine metabolism by nervous activity. The neurodevelopment studies proposed in this grant, which cover competition of nerve cells for their selective targets and the role of cell death in embryogenesis, are significant to one of the major unsolved problems in neurobiology, i.e., the mechanism by which cells acquire and maintain specific connections with each other. The study will be done in a simple avian neuroeffector system, which consists of central neuron in the accessory nucleus of the brain, the connecting cells in the ciliary ganglion, and its effector organs in the eye. The research will be centered on the pre- and postsynaptic contacts, the interaction between these elements, and the modifications of these interactions by experimental manipulation of their central and peripheral connections. The work will be a joint effort involving electrophysiological, electron microscopic, histochemical and biochemical techniques. The experiments will be done in embryonic as well as mature cells, and they will be carried out in isolated superfused preparations and in tissue and organ cultures of the same elements. BIBLIOGRAPHIC REFERENCES: Influence of nerve section, axonal flow and activity on acetylcholine synthesis in nerve terminals. R. Beach and G. Pilar, 1977. Fed. Proc. 36:486. Mechanisms regulating acetylcholine synthesis at the neuromuscular junction. K. Vaca and G. Pilar, 1977. Neuroscience Abstracts 3, in press.